One percent of humans worldwide are afflicted with rheumatoid arthritis (RA), a relentless, progressive disease causing severe swelling, pain, and eventual deformity and destruction of joints. According to the Arthritis Foundation, RA currently affects over two million Americans, of which women are three times more likely to be afflicted. RA is characterized by inflammation of the lining of the joints and/or other internal organs, and the presence of elevated numbers of lymphocytes and high levels of proinflammatory cytokines.
For many years, corticosteroids have been used extensively as a first line treatment of RA. Unfortunately, corticosteroid therapy is often accompanied by numerous side effects, including bone loss, increased susceptibility to infection, osteoporosis, and peptic ulcers. Additionally, weaning patients from corticosteroids can be difficult and relapses of articular degeneration are frequent once the steroid is discontinued. These steroidal compounds are potent inhibitors of tumor necrosis factor (TNF). Therefore, all TNF inhibitors are not desired clinical candidates.